The aim of this study was to compare the plasma concentration profile, mammary blood flow response and transfer into milk of intact IGF-I with that of its truncated analogue, des(1–3)IGF-I (des-IGF-I). Each peptide was infused for 24 h into the pudic artery supplying one mammary gland of lactating goats (n=5). Concentrations of IGF-I in plasma (from the jugular vein) rose rapidly during infusion of IGF-I or des-IGF-I to reach 510±62 and 640±32 ng/ml (mean ± s.e.m.) respectively, compared with 262±35 ng/ml after a similar infusion of saline. Ligand blotting analysis indicated a significant increase in the intensity of [125I]IGF-I binding to the 40–43 kDa doublet (binding protein-3 (BP-3), P<0·01) and the band at 31 kDa (P<0·05) during infusion of either IGF-I or des-IGF-I, as compared with saline. Furthermore des-IGF-I induced a significant increase in intensity of binding to the 35 and 24 kDa bands, but IGF-I did not. Whereas [125I]IGF-I was distributed between BP-3 and the other binding proteins, [125I]des-IGF-I bound exclusively to BP-3.
Mammary blood flow (MBF) increased 48±6% after 12 h of infusion of des-IGF-I, compared with an increase of 22±6% during IGF-I. The difference in response was significant at P<0·05. In addition, more IGF-I was secreted into the milk of the infused than the non-infused gland during either infusion of IGF-I or des-IGF-I. This difference between glands was greater (P<0·05) during des-IGF-I compared with IGF-I infusion, suggesting greater uptake of des-IGF-I by the gland compared with IGF-I, when infused locally. These findings indicate a greater bioactivity of des-IGF-I compared with IGF-I when infused locally into the mammary gland and may be explained by the different pattern of association of the two peptides with different binding proteins. The similar plasma profile and pharmacokinetics for IGF-I and desIGF-I during their 24-h continuous infusion of des-IGF-I or IGF-I is in contrast to results reported for a single injection of the peptides, probably relating to the ability of des-IGF-I to induce and bind to BP-3.
Journal of Endocrinology (1995) 144, 99–107